Use of combination therapy with acetaminophen and ibuprofen for closure of the patent ductus arteriosus in preterm neonates

Abstract Objective To compare effectiveness and safety of combination therapy (acetaminophen and ibuprofen) to monotherapy (ibuprofen, indomethacin, or acetaminophen alone) in treatment of the patent ductus arteriosus (PDA) in premature neonates. Methods This was a retrospective cohort study of neonates admitted to a tertiary-level neonatal intensive care unit. Included neonates were born at <32 weeks gestation and received pharmacotherapy for PDA closure. Based on the primary therapy received, our cohort was divided into the following four groups: indomethacin alone, ibuprofen alone, acetaminophen alone, and ibuprofen and acetaminophen (in combination). Baseline characteristics, effectiveness, safety, neonatal mortality, and morbidities rates between these groups were compared. Results One hundred and forty neonates were analyzed; 17 received combination therapy, and 123 neonates received monotherapy: 22 (17.9%) ibuprofen, 29 (23.6%) acetaminophen, and 72 (58.5%) indomethacin. The PDA closure rates were 41.7% for indomethacin, 41.2% for combination therapy, 37.9% for acetaminophen, and 31.8% for ibuprofen (P=0.100). Rates of adverse effects were comparable between the groups. Conclusion The rate of ductal closure was not different between combination therapy and monotherapy. The study did not demonstrate any increased adverse effects in the combination group. Future well-designed prospective clinical trials are needed to guide clinical practice.

Download Full-text

Paracetamol vs Ibuprofen in Hemodynamically Significant Patent Ductus Arteriosus (HsPDA) in Preterms: A Randomized Controlled Trial

Asian Journal of Pediatric Research ◽

10.9734/ajpr/2020/v3i130118 ◽

2020 ◽

pp. 6-13

Author(s):

Hinal A. Sinol ◽

Alpa N. Parekh ◽

Jayendra R. Gohil ◽

Mehul Gosai

Keyword(s):

Adverse Effects ◽

Patent Ductus Arteriosus ◽

Preterm Infants ◽

Discharge Rate ◽

Controlled Trial ◽

Ductus Arteriosus ◽

Preterm Neonates ◽

Ductal Closure ◽

Ibuprofen Group ◽

Patent Ductus

Background and Objective: Hemodynamically significant patent ductus arteriosus (HsPDA) is a common cause of morbidity in preterm infants. Indomethacin and Ibuprofen, which are cyclo-oxygenase (COX) 1, 2 inhibitors are commonly used drugs for closure of HsPDA. As, Ibuprofen has several contraindications, we designed study using oral paracetamol (a peroxidase inhibitor) and compared with oral ibuprofen, for efficacy and safety in relation to closure of HsPDA in preterm infants. Methods: 140 preterm infants (gestational age less than 32 weeks) with HsPDA (confirmed by 2D Echo) were randomly assigned in two groups and received first course of either oral paracetamol (70) or ibuprofen (70). The need for a second course was determined by 2D Echo evaluation. Parameters studied were rate of ductal closure, any adverse effects and discharge rate. Results: Both groups were similar in term of ductal closure after first course (p=0.46) and second course (p=0.59). However, 22 from Ibuprofen group and only 2 from PCM group developed adverse effects (p<0.001). From paracetamol group 58 were discharged, and 12 died; while from ibuprofen group 46 discharged, 24 died (p=0.03). Conclusion: Paracetamol for HsPDA in preterm neonates was associated with good efficacy and better safety; and less deaths, as compared to ibuprofen.

Download Full-text

Surgical ligation of patent ductus arteriosus in preterm neonates weighing less than 1,500 g: A 9-year single center experience

10.21203/rs.3.rs-17138/v2 ◽

2020 ◽

Author(s):

Jun Ho Lee ◽

Hyun Ju Lee ◽

Hyun-Kyung Park ◽

Ja-Hye Ahn ◽

Hee Sun Kim ◽

...

Keyword(s):

Surgical Treatment ◽

Patent Ductus Arteriosus ◽

Neonatal Intensive Care ◽

Ductus Arteriosus ◽

Preterm Neonates ◽

Surgical Ligation ◽

Single Center Experience ◽

Ductal Closure ◽

Low Incidence ◽

Patent Ductus

Abstract Background: The aim of this study was to determine the feasibility and outcomes of early surgical ligation in preterm neonates with hemodynamically significant patent ductus arteriosus (HSPDA) and to investigate predictors for surgical treatment after unsuccessful medical management.Methods: Medical records from the neonatal intensive care unit of Hanyang University Seoul Hospital from January 2010 to December 2018 were retrospectively reviewed. 233 preterm neonates weighing less than 1,500 g with HSPDA were enrolled in our study. Of these preterm neonates, 134 underwent surgical ligation and were subdivided into the early ligation group (n = 49; within 10 days of age) and the late ligation group (n = 85; after 10 days of age).Results: The mean gestational age and birth weight were significantly lower in the patent ductus arteriosus (PDA) ligation group than in the Non-ligation group (p < 0.001). PDA ductal diameter > 2.0 mm (p < 0.001), low Apgar score at 5 minutes (p = 0.033), and chorioamnionitis (p = 0.037) were the predictors for receiving surgical treatment for PDA. Early ligation was significantly associated with a low incidence of culture-proven sepsis (p = 0.004), mechanical ventilator time > 4 weeks (p = 0.007), necrotizing enterocolitis stage (NEC) ≥ III (p = 0.022), and intraventricular hemorrhage (IVH) grade ≥ III (p = 0.035).Conclusions: Early surgical ligation minimizes the adverse effects of HSPDA in predicted preterm neonates who subsequently require surgical treatment for PDA. This result suggests that in preterm neonates weighing less than 1,500 g with HSPDA that is unresponsive to medical treatment, delayed ductal closure should be avoided to reduce severe NEC, severe IVH, culture-proven sepsis, and facilitate earlier endotracheal extubation.

Download Full-text

The Comparison Between Intravenous Acetaminophen Versus Oral Ibuprofen in Preterm Newborns With Patent Ductus Arteriosus: A Clinical Trial

ACTA MEDICA IRANICA ◽

10.18502/acta.v58i12.5155 ◽

2021 ◽

Author(s):

Behzad Mohammadpour Ahranjani ◽

Hosein Dalil ◽

Zeinab Harif Nashtifani ◽

Mamak Shariat ◽

Mohammadrafie Khorgami

Keyword(s):

Side Effects ◽

Patent Ductus Arteriosus ◽

Ductus Arteriosus ◽

Clinical Status ◽

Preterm Neonates ◽

Intravenous Acetaminophen ◽

Ductal Closure ◽

Oral Ibuprofen ◽

Preterm Newborns ◽

Patent Ductus

Oral ibuprofen has been known as a conventional treatment for closing patent ductus arteriosus (PDA) in preterm newborns. Since the use of it might lead to various side effects, other treatments needed to be evaluated. Therefore in a prospective study, we compared the efficacy and safety of intravenous acetaminophen versus oral ibuprofen for the closure of PDA. In this study which was done prospectively and under control, 50 preterm neonates with gestational ages and weights less than 37 weeks old and 2500 grams, respectively, who had PDA, large enough hemodynamically, were included in the study. The patients were divided into two groups: A (intravenous acetaminophen) & B (oral ibuprofen). The two groups were given at most two 3-day courses of the medication (the second course if necessary) and evaluated at the end of each course by echocardiography so as to determine the response to the treatment at each step. The rate of ductal closure, the need for additional treatment, side effects, complications and the newborn’s clinical status were recorded. The rate of ductal closure in the both groups after one course of treatment was similar and showed no meaningful significance statistically (P=0.306). But that of the side effects was much higher in group B with a P=0.021. Intravenous Acetaminophen is not only as efficacious as oral Ibuprofen for the treatment of PDA in preterm infants, but also is less likely to lead to side effects and complications.

Download Full-text

Assessing the clinical significance of echocardiograms in determining treatment of patent ductus arteriosus in neonates

Journal of Neonatal-Perinatal Medicine ◽

10.3233/npm-170122 ◽

2020 ◽

Vol 13 (3) ◽

pp. 345-350

Author(s):

D. Youssef ◽

M.N. Flores ◽

E. Ebrahim ◽

K. Eshak ◽

J. Westerink ◽

...

Keyword(s):

Patent Ductus Arteriosus ◽

Neonatal Intensive Care ◽

Ductus Arteriosus ◽

Preterm Neonates ◽

Control Group ◽

Retrospective Case ◽

Group A ◽

Group B ◽

Clinical Measures ◽

Patent Ductus

BACKGROUND: To evaluate the utility of echocardiogram (ECHO) in detection and treatment of patent ductus arteriosus (PDA) and hemodynamically significant PDA (hsPDA) in preterm neonates. METHODS: This was a retrospective case-control study of all preterm infants born or admitted to the level III Neonatal Intensive Care Unit in McMaster Children’s Hospital from January 2009 to January 2013. These cases were further classified into the following sub-groups: group A) hsPDA confirmed on ECHO; and the control, group B) PDA (but not hemodynamically significant) confirmed on ECHO. Patients without an ECHO were excluded from all analyses. The primary outcome was incidence of treatment for PDA. RESULTS: PDA treatment was administered in 83.3% and 11.2% of patients in groups A and B respectively (P < 0.05). Among patients with a hsPDA within group A, 17% did not receive treatment, while 11% of patients with non-hemodynamically significant PDA received treatment for the PDA. Within the cohort of patients who received treatment for a hsPDA, gestational age below 35 weeks as well as murmurs heard on auscultation were both found to be predictors of treatment. CONCLUSION: While the ECHO remains the gold standard for detecting pathological PDA, there is evidence that other traditional clinical measures continue to guide clinical practice and treatment decisions. Further research is required to gain an understanding of how clinical measures and ECHO may be used in conjunction to optimize resource utilization.

Download Full-text

Surgical Intervention in Preterm Neonates with Patent Ductus Arteriosus

Current Pediatric Reviews ◽

10.2174/157339631202160506002405 ◽

2016 ◽

Vol 12 (2) ◽

pp. 123-125

Author(s):

Marcus P. Haw

Keyword(s):

Patent Ductus Arteriosus ◽

Surgical Intervention ◽

Ductus Arteriosus ◽

Preterm Neonates ◽

Patent Ductus

Download Full-text

Patent ductus arteriosus in preterm infants; experience of a tertiary referral neonatal intensive care unit: prevalence, complications, and management

Egyptian Pediatric Association Gazette ◽

10.1186/s43054-020-00046-8 ◽

2020 ◽

Vol 68 (1) ◽

Author(s):

Reem M. Soliman ◽

Fatma Alzahraah Mostafa ◽

Antoine Abdelmassih ◽

Elham Sultan ◽

Dalia Mosallam

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Side Effects ◽

Patent Ductus Arteriosus ◽

Neonatal Intensive Care Unit ◽

Preterm Infants ◽

Neonatal Intensive Care ◽

Ductus Arteriosus ◽

Patent Ductus

Abstract Background Patent ductus arteriosus poses diagnostic and therapeutic dilemma for clinicians, diagnosis of persistent PDA, and determination of its clinical and hemodynamic significance are challenging. The aim of this study is to determine the prevalence of PDA in preterm infants admitted to our NICU, to report cardiac and respiratory complications of PDA, and to study the management strategies and their subsequent outcomes. Result Echocardiography was done for 152 preterm babies admitted to neonatal intensive care unit (NICU) on day 3 of life. Eighty-seven (57.2%) preterms had PDA; 54 (62.1%) non-hemodynamically significant PDA (non-hsPDA), and 33 (37.9%) hemodynamically significant PDA. Hemodynamically significant PDA received medical treatment (paracetamol 15 mg/kg/6 h IV for 3 days). Follow-up echocadiography was done on day 7 of life. Four babies died before echo was done on day 7. Twenty babies (68.9%) achieved closure after 1st paracetamol course. Nine babies received 2nd course paracetamol. Follow-up echo done on day 11 of life showed 4 (13.7%) babies achieved successful medical closure after 2nd paracetamol course; 5 babies failed closure and were assigned for surgical ligation. The group of non-hsPDA showed spontaneous closure after conservative treatment. Pulmonary hemorrhage was significantly higher in hsPDA group. Mortality was higher in hsPDA group than non-hsPDA group. Conclusion Echocardiographic evaluation should be done for all preterms suspected clinically of having PDA. We should not expose vulnerable population of preterm infants to medication with known side effects unnecessarily; we should limit medical closure of PDA to hsPDA. Paracetamol offers several important therapeutic advantages options being well tolerated and having more favorable side effects profile.

Download Full-text